HDL biology
ApoCI deficiency doubles CETP-driven HDL cholesteryl ester depletion in transgenic mice (J Biol Chem 2002)
Original title: Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes mediated by human cholesteryl ester transfer protein (CETP) in CETP transgenic/ApoCI-knocked out mice
Researchers crossed mice expressing human CETP (HuCETPTg) with apolipoprotein CI-knockout (apoCI-KO) mice to test whether apoCI restrains CETP activity in vivo. Total cholesterol fell modestly in HuCETPTg mice versus controls (-13%, not significant) but significantly more when CETP was expressed on an apoCI-deficient background (-28%, p<0.05); VLDL cholesteryl ester content rose 6.1-fold in HuCETPTg/apoCI-KO mice versus a non-significant 2.7-fold rise in HuCETPTg mice alone (p<0.05). HDL cholesteryl ester content and cholesteryl ester-to-triglyceride ratio fell about 50% in HuCETPTg/apoCI-KO mice versus controls (p<0.05), with intermediate -20% changes in HuCETPTg mice, and HDL particle diameter shrank correspondingly (8.68 nm versus 8.83 nm, p<0.05). Purified apoCI inhibited cholesteryl ester exchange in vitro, and CETP specific activity was significantly higher in the apoCI-deficient state (173 versus 72 pmol/ug/h, p<0.05), with apoCI-KO HDL binding CETP more readily than control HDL. The authors conclude these findings provide direct in vivo support for apoCI as a potent, specific physiological inhibitor of CETP.
Original abstract
Transgenic mice expressing human cholesteryl ester transfer protein (HuCETPTg mice) were crossed with apolipoprotein CI-knocked out (apoCI-KO) mice. Although total cholesterol levels tended to be reduced as the result of CETP expression in HuCETPTg heterozygotes compared with C57BL6 control mice (-13%, not significant), a more pronounced decrease (-28%, p < 0.05) was observed when human CETP was expressed in an apoCI-deficient background (HuCETPTg/apoCI-KO mice). Gel permeation chromatography analysis revealed a significant, 6.1-fold rise (p < 0.05) in the cholesteryl ester content of very low density lipoproteins in HuCETPTg/apoCI-KO mice compared with control mice, whereas the 2.7-fold increase in HuCETPTg mice did not reach the significance level in these experiments. Approximately 50% decreases in the cholesteryl ester content and cholesteryl ester to triglyceride ratio of high density lipoproteins (HDL) were observed in HuCETPTg/apoCI-KO mice compared with controls (p < 0.05 in both cases), with intermediate -20% changes in HuCETPTg mice. The cholesteryl ester depletion of HDL was accompanied with a significant reduction in their mean apparent diameter (8.68 +/- 0.04 nm in HuCETPTg/apoCI-KO mice versus 8.83 +/- 0.02 nm in control mice; p < 0.05), again with intermediate values in HuCETPTg mice (8.77 +/- 0.04 nm). In vitro purified apoCI was able to inhibit cholesteryl ester exchange when added to either total plasma or reconstituted HDL-free mixtures, and coincidently, the specific activity of CETP was significantly increased in the apoCI-deficient state (173 +/- 75 pmol/microg/h in HuCETPTg/apoCI-KO mice versus 72 +/- 19 pmol/microg/h in HuCETPTg, p < 0.05). Finally, HDL from apoCI-KO mice were shown to interact more readily with purified CETP than control HDL that differ only by their apoCI content. Overall, the present observations provide direct support for a potent specific inhibition of CETP by plasma apoCI in vivo.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.